The goal of the proposal is to determine the role of fibronectin in the differentiation of chondrocytes. Since differentiation of mesenchymal cells into chondrocytes is one of the earliest steps in endochondral bone formation and bone fracture repair, the studies proposed should lead to an increased understanding of chondrogenic expression and bone morphogenesis. It has been demonstrated that cellular fibronectin is one of the chief determinants of chondrogenic expression. In the presence of fibronectin, chondroblasts remain undifferentiated; while the removal of fibronectin or the addition of antibodies of fibronectin results in chondrogenic expression. Based on our current understanding of the molecular biology of fibronectin, we propose to examine the molecular mechanism involved in the control of chondrogenic expression by fibronectin. We will determine the region of fibronectin responsible for its effects on the differentiation of chondrocytes by the isolation of appropriate proteolytic fragments of fibronectin. The fibronectin fragment isolated will be analyzed in order to determine the identity of the receptor responsible for chondrogenic expression. The cell surface molecular responsible for the differentiative action of fibronectin will be isolated. Intrinsic membrane molecules which participate in fibronectin-mediated cell adhesion will be examined by biochemical and biophysical means.